Effects of blood lipids and lipid-modifying drugs on intracranial aneurysms.

Abstract

We used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-modifying drugs on intracranial aneurysm (IA). Genetic variants for the effects of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, and triglycerides and targets for lipid-modifying drugs were selected from the genome-wide discovery analyses of the UK Biobank. Summary-level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. Univariate MR analyses showed that the HDL-C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715-0.932, p= 0.003) and ruptured IA (rIA; OR=0.775, 95% CI=0.663-0.906, p= 0.001). The multivariate MR-inverse variance weighted analysis showed that the HDL-C was negatively correlated with IA (OR=0.655, 95% CI=0.434-0.988, p= 0.043) and rIA (OR=0.563, 95% CI=0.347-0.913, p= 0.02), and the LDL-C was negatively correlated with IA (OR=0.402, 95% CI=0.191-0.848, p= 0.017) and rIA (OR=0.376, 95% CI=0.160-0.883, p= 0.025). Using genetic proxies of known lipid-modifying drugs, we found that the increased HDL-C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR=0.852, 95% CI=0.747-0.973, p= 0.018), and the decreased LDL-C with 3-hydroxy-3-methylglutaryl-coenzyme A reductase proxies was associated with increased risk of IA (OR=1.772, 95% CI=1.080-2.908, p= 0.024) and rIA (OR=1.856, 95% CI=1.022-3.371, p= 0.042). Genetically determined HDL-C and LDL-C reduce the risk of IA and rIA. The effects of different lipid-modifying drugs on IA need to be further investigated.